Pathological cutaneous manifestation affects up to 70% of people with type II diabetes mellitus (T2D). This involves especially the diabetic foot syndrome, bacterial and fungal infections and slowed wound healing. The cumulation of methylglyoxal and by that higher levels of advanced glycation end-products (AGE) in the skin is considered to highly contribute skin pathology in T2D patients. A pilot study with 12 diabetic and 12 non-diabetic individuals was carried out to investigate the in vivo levels of glucose and AGEs, as well as the in vivo activity of the MGO-detoxifying glyoxalase I in suction blister fluid (SBF). For the first time, it was presented that the glucose level in the SBF of diabetics was increased compared to non-diabetic people, in vivo. Remarkably, the glyoxalase I activity from lysed epidermal roofs in diabetics and non-diabetic individuals was comparable. The current paradigm that AGEs result from increased production of MGO due to reduced expression and / or reduced activity of MGO-detoxifying glyoxalase I could therefore not be endorsed by these observations. Furthermore, a multiplex analysis of 25 proteins involved in T2D pathology detected several proteins with significantly increased expression levels in SBF of diabetics that could serve as potential biomarkers, including Vascular Adhesion Protein-1 (VAP1). VAP1 expresses amine oxidase activity, which makes aldehydes from primary amines, resulting in high levels of MGO. Based on these findings a new hypothesis was introduced that increased levels of VAP1 (could) contribute to elevated MGO levels in the skin. Furthermore, the influence of type II diabetes mellitus on the skin microbiome was investigated using the skin wipe down method and 16S rRNA sequencing. Alpha and beta diversity was increased in the diabetic group. In addition, diabetics and non-diabetic people were composed differently, with the most common phylum in diabetics and between the groups being the firmicutes. In addition, it was discovered that the glucose level in suction blister fluids was increased in diabetics, which could contribute to a deviating microbial phenotype. Long-term reductions in diversity have so far been associated with pathological phenotypes only. It was therefore very striking to find an increased diversity in the diabetic group compared to the non-diabetic group. In addition, it was possible to identify possible indicator OTUs for each group (9 in the diabetic and 1 in the non-diabetic group).